Displaying publications 61 - 80 of 522 in total

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  1. Neuroprotective effects of brain-derived neurotrophic factor against amyloid beta 1-40-induced retinal and optic nerve damage
    Mohd Lazaldin MA, Iezhitsa I, Agarwal R, Bakar NS, Agarwal P, Mohd Ismail N
    Eur J Neurosci, 2020 06;51(12):2394-2411.
    PMID: 31883161 DOI: 10.1111/ejn.14662
    Brain-derived neurotrophic factor (BDNF) could be considered a potential neuroprotective therapy in amyloid beta (Aβ)-associated retinal and optic nerve degeneration. Hence, in this study we investigated the neuroprotective effect of BDNF against Aβ1-40-induced retinal and optic nerve injury. In this study, exposure to Aβ1-40 was associated with retinal and optic nerve injury. TUNEL staining showed significant reduction in the apoptotic cell count in the BDNF-treated group compared with Aβ1-40 group. H&E-stained retinal sections also showed a striking reduction in neuronal cells in the ganglion cell layer (GCL) of retinas fourteen days after Aβ1-40 exposure. By contrast, number of retinal cells was preserved in the retinas of BDNF-treated animals. After Aβ1-40 exposure, visible axonal swelling was observed in optic nerve sections. However, the BDNF-treated group showed fewer changes in optic nerve; axonal swelling was less frequent and less marked. In the present study, exposure to Aβ was associated with oxidative stress, whereas levels of retinal glutathione (GSH), superoxide dismutase (SOD) and catalase were significantly increased in BDNF-treated than in Aβ1-40-treated rats. Both visual object recognition tests using an open-field arena and a Morris water maze showed that BDNF improved rats' ability to recognise visual cues (objects with different shapes) after Aβ1-40 exposure, thus demonstrating that the visual performance of rats was relatively preserved following BDNF treatment. In conclusion, intravitreal treatment with BDNF prevents Aβ1-40-induced retinal cell apoptosis and axon loss in the optic nerve of rats by reducing retinal oxidative stress and restoring retinal BDNF levels.
    Matched MeSH terms: Amyloid beta-Peptides/toxicity
  2. Fulltext Cognitive trajectories of patients with focal ß-amyloid deposition
    Kim SE, Lee B, Jang H, Chin J, Khoo CS, Choe YS, et al.
    Alzheimers Res Ther, 2021 02 19;13(1):48.
    PMID: 33608041 DOI: 10.1186/s13195-021-00787-7
    BACKGROUND: The presence of ß-amyloid (Aß) in the brain can be identified using amyloid PET. In clinical practice, the amyloid PET is interpreted based on dichotomous visual rating, which renders focal Aß accumulation be read as positive for Aß. However, the prognosis of patients with focal Aß deposition is not well established. Thus, we investigated cognitive trajectories of patients with focal Aß deposition.

    METHODS: We followed up 240 participants (112 cognitively unimpaired [CU], 78 amnestic mild cognitive impairment [aMCI], and 50 Alzheimer's disease (AD) dementia [ADD]) for 2 years from 9 referral centers in South Korea. Participants were assessed with neuropsychological tests and 18F-flutemetamol (FMM) positron emission tomography (PET). Ten regions (frontal, precuneus/posterior cingulate (PPC), lateral temporal, parietal, and striatum of each hemisphere) were visually examined in the FMM scan, and participants were divided into three groups: No-FMM, Focal-FMM (FMM uptake in 1-9 regions), and Diffuse-FMM. We used mixed-effects model to investigate the speed of cognitive decline in the Focal-FMM group according to the cognitive level, extent, and location of Aß involvement, in comparison with the No- or Diffuse-FMM group.

    RESULTS: Forty-five of 240 (18.8%) individuals were categorized as Focal-FMM. The rate of cognitive decline in the Focal-FMM group was faster than the No-FMM group (especially in the CU and aMCI stage) and slower than the Diffuse-FMM group (in particular in the CU stage). Within the Focal-FMM group, participants with FMM uptake to a larger extent (7-9 regions) showed faster cognitive decline compared to those with uptake to a smaller extent (1-3 or 4-6 regions). The Focal-FMM group was found to have faster cognitive decline in comparison with the No-FMM when there was uptake in the PPC, striatum, and frontal cortex.

    CONCLUSIONS: When predicting cognitive decline of patients with focal Aß deposition, the patients' cognitive level, extent, and location of the focal involvement are important.

    Matched MeSH terms: Amyloid beta-Peptides/metabolism
  3. Cell-Penetrating Peptides: Correlation between Peptide-Lipid Interaction and Penetration Efficiency
    Her Choong F, Keat Yap B
    Chemphyschem, 2021 03 03;22(5):493-498.
    PMID: 33377300 DOI: 10.1002/cphc.202000873
    Cell-penetrating peptides are used in the delivery of peptides and biologics, with some cell-penetrating peptides found to be more efficient than others. The exact mechanism of how they interact with the cell membrane and penetrate it, however, remains unclear. This study attempts to investigate the difference in free energy profiles of three cell-penetrating peptides (TAT, CPP1 and CPP9) with a model lipid bilayer (DOPC) using molecular dynamics pulling simulations with umbrella sampling. Potential mean force (PMF) and free energy barrier between the peptides and DOPC are determined using WHAM analysis and MM-PBSA analysis, respectively. CPP9 is found to have the smallest PMF value, followed by CPP1 and TAT, consistent with the experimental data. YDEGE peptide, however, does not give the highest PMF value, although it is a non-cell-permeable peptide. YDEGE is also found to form water pores, alongside with TAT and CPP9, suggesting that it is difficult to distinguish true water pore formation from artefacts arising from pulling simulations. On the contrary, free energy analysis of the peptide-DOPC complex at the lipid-water interface with MM-PBSA provides results consistent with experimental data with CPP9 having the least interaction with DOPC and lowest free energy barrier, followed by CPP1, TAT and YDEGE. These findings suggest that peptide-lipid interaction at the lipid-water interface has a direct correlation with the penetration efficiency of peptides across the lipid bilayer.
    Matched MeSH terms: Peptides/metabolism*
  4. Peptide inhibitors of Macrobrachium rosenbergii nodavirus
    Thong QX, Wong CL, Ooi MK, Kueh CL, Ho KL, Alitheen NB, et al.
    J Gen Virol, 2018 09;99(9):1227-1238.
    PMID: 30041713 DOI: 10.1099/jgv.0.001116
    Macrobrachium rosenbergii nodavirus (MrNv) causes white tail disease (WTD) in giant freshwater prawns, which leads to devastating economic losses in the aquaculture industry. Despite extensive research on MrNv, there is still no antiviral agent to treat WTD. Thus, the main aim of this study was to identify potential anti-MrNv molecules. A 12-mer phage-displayed peptide library was biopanned against the MrNv virus-like particle (VLP). After four rounds of biopanning, two dominant phages harbouring the amino acid sequences HTKQIPRHIYSA and VSRHQSWHPHDL were selected. An equilibrium binding assay in solution was performed to determine the relative dissociation constant (KDrel) of the interaction between the MrNv VLP and the selected fusion phages. Phage-HTKQIPRHIYSA has a KDrel value of 92.4±22.8 nM, and phage-VSRHQSWHPHDL has a KDrel value of 12.7±3.8 nM. An in-cell elisa was used to determine the inhibitory effect of the synthetic peptides towards the entry of MrNv VLP into Spodoptera frugiperda (Sf9) cells. Peptides HTKQIPRHIYSA and VSRHQSWHPHDL inhibited the entry of the MrNv VLP into Sf9 cells with IC50 values of 30.4±3.6 and 26.5±8.8 µM, respectively. Combination of both peptides showed a significantly higher inhibitory effect with an IC50 of 4.9±0.4 µM. An MTT assay revealed that the viability of MrNv-infected cells increased to about 97 % in the presence of both peptides. A real-time RT-PCR assay showed that simultaneous application of both peptides significantly reduced the number of MrNv per infected cell, from 97±9 to 11±4. These peptides are lead compounds which can be further developed into potent anti-MrNv agents.
    Matched MeSH terms: Peptides/pharmacology*
  5. Fulltext Cytotoxicity effect of oil palm (Elaeis guineensis) kernel protein hydrolysates
    Chang, S.K., Hamajima, H., Amin, I., Yanagita, T., Mohd. Esa, N., Baharuldin, M.T.H.
    International Food Research Journal, 2014;21(3):909-914.
    MyJurnal
    This study was conducted to ascertain the cytotoxicity effect of oil palm (Elaeis guineensis) kernel protein hydrolysates (OPKHs) produced from its protein isolate. A modified microplate titer WST-1 [2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium] assay was used to investigate the cytotoxicity of hydrolysates produced from protease and pepsin-pancreatin hydrolysis at various concentrations (0.1, 1, 10, 100 μg/ml and 1 mg/ml) using HepG2 cell model. Additionally, peptide stimulation test using OPKHs at 1 mg/ml was carried out to investigate whether OPKHs could serve as growth factor for HepG2 cells other than affecting its viability. As a result, oleic acid appeared to normalize the WST-1 readings of HepG2 cells treated with both hydrolysates at 1 mg/ml. The presence of amino acids in OPKHs could stimulate the growth and prolongs the viability of HepG2 cells. Both OPKHs were non-cytotoxic to HepG2 cells at all tested concentrations even at high concentrations. This study indicated that pepsin-pancreatin and protease hydrolysates produced from oil palm kernel protein were non-cytotoxic on HepG2 cells.
    Matched MeSH terms: Peptides; Intercellular Signaling Peptides and Proteins
  6. Peptide Cross-Linked Poly(2-oxazoline) as a Sensor Material for the Detection of Proteases with a Quartz Crystal Microbalance
    Ahmad N, Colak B, Gibbs MJ, Zhang DW, Gautrot JE, Watkinson M, et al.
    Biomacromolecules, 2019 07 08;20(7):2506-2514.
    PMID: 31244015 DOI: 10.1021/acs.biomac.9b00245
    Inflammatory conditions are frequently accompanied by increased levels of active proteases, and there is rising interest in methods for their detection to monitor inflammation in a point of care setting. In this work, new sensor materials for disposable single-step protease biosensors based on poly(2-oxazoline) hydrogels cross-linked with a protease-specific cleavable peptide are described. The performance of the sensor material was assessed targeting the detection of matrix metalloproteinase-9 (MMP-9), a protease that has been shown to be an indicator of inflammation in multiple sclerosis and other inflammatory conditions. Films of the hydrogel were formed on gold-coated quartz crystals using thiol-ene click chemistry, and the cross-link density was optimized. The degradation rate of the hydrogel was monitored using a quartz crystal microbalance (QCM) and showed a strong dependence on the MMP-9 concentration. A concentration range of 0-160 nM of MMP-9 was investigated, and a lower limit of detection of 10 nM MMP-9 was determined.
    Matched MeSH terms: Peptides/chemistry*
  7. Epinecidin-1, a marine antifungal peptide, inhibits Botrytis cinerea and delays gray mold in postharvest peaches
    Fan L, Wei Y, Chen Y, Jiang S, Xu F, Zhang C, et al.
    Food Chem, 2023 Mar 01;403:134419.
    PMID: 36191421 DOI: 10.1016/j.foodchem.2022.134419
    This study investigatedthe mechanism of epinecidin-1 against Botrytis cinerea, in vitro, and its effectiveness at inhibiting gray mold on postharvest peach fruit. We found that in vitro, epinecidin-1 had significantly greater antifungal activity against B. cinerea than either clavanin-A or mytimycin, two other marine derived antimicrobial peptides that we tested. Its antifungal activity was heat-resistant (15 min at 40-100 °C) and tolerant to lower concentrations of cations (<100 mM Na+, K+; <10 mM Ca2+). Epinecidin-1 interacted directly with B. cinerea genomic DNA, and that in mycelia, epinecidin-1 exposure induced accumulation of intracellular ROS and increased the permeability of cell membranes resulting in leakage of nucleic acids and aberrant cell morphology. Meanwhile, 200 μM of epinecidin-1 had a significant inhibitory effect on gray mold injected into peach fruit. These results suggested that epinecidin-1 showed promise as a potential method for controlling postharvest gray mold in peaches.
    Matched MeSH terms: Peptides/pharmacology
  8. GR15 peptide of S-adenosylmethionine synthase (SAMe) from Arthrospira platensis demonstrated antioxidant mechanism against H2O2 induced oxidative stress in in-vitro MDCK cells and in-vivo zebrafish larvae model
    Velayutham M, Guru A, Arasu MV, Al-Dhabi NA, Choi KC, Elumalai P, et al.
    J Biotechnol, 2021 Dec 10;342:79-91.
    PMID: 34751134 DOI: 10.1016/j.jbiotec.2021.10.010
    GR15 is a short molecule or peptide composed of aliphatic amino acids and possesses to have antioxidant properties. The GR15, 1GGGAFSGKDPTKVDR15 was identified from the protein S-adenosylmethionine synthase (SAMe) expressed during the sulfur departed state of Arthrospira platensis (spirulina or cyanobacteria). The in-silico assessment and the structural features of GR15 showed its antioxidant potency. Real-time PCR analysis found the up-regulation of ApSAMe expression on day 15 against oxidative stress due to 10 mM H2O2 treatment in A. platensis (Ap). The antioxidant activity of GR15 was accessed by the cell-free antioxidant assays such as ABTS, SARS, HRAS and NO; the results showed dose-dependent antioxidant activity. The toxicity assay was performed in both in vitro and in vivo models, in which peptide does not exhibit any toxicity in MDCK cell and zebrafish embryos. The intercellular ROS reduction potential of GR15 peptide was also investigated in both in vitro and in vivo models including LDH assay, antioxidant enzymes (SOD and CAT), and fluorescent staining assay (DCFDA, Hochest and Acridine orange sting) was performed; the results showed that the GR15 peptide was effectively reduced the ROS level. Further, RT-PCR demonstrated that GR15 enhanced the antioxidant property and also up-regulated the antioxidant gene, thus reduced the ROS level in both in vitro and in vivo models. Based on the results obtained from this study, we propose that GR15 has the potential antioxidant ability; hence further research can be directed towards the therapeutic product or drug development against disease caused by oxidative stress.
    Matched MeSH terms: Peptides/metabolism
  9. Fulltext Effects of Ultrasound Assisted Extraction in Conjugation with Aid of Actinidin on the Molecular and Physicochemical Properties of Bovine Hide Gelatin
    Ahmad T, Ismail A, Ahmad SA, Khalil KA, Leo TK, Awad EA, et al.
    Molecules, 2018 Mar 22;23(4).
    PMID: 29565325 DOI: 10.3390/molecules23040730
    Actinidin was used to pretreat the bovine hide and ultrasonic wave (53 kHz and 500 W) was used for the time durations of 2, 4 and 6 h at 60 °C to extract gelatin samples (UA2, UA4 and UA6, respectively). Control (UAC) gelatin was extracted using ultrasound for 6 h at 60 °C without enzyme pretreatment. There was significant (p < 0.05) increase in gelatin yield as the time duration of ultrasound treatment increased with UA6 giving the highest yield of 19.65%. Gel strength and viscosity of UAC and UA6 extracted gelatin samples were 627.53 and 502.16 g and 16.33 and 15.60 mPa.s, respectively. Longer duration of ultrasound treatment increased amino acids content of the extracted gelatin and UAC exhibited the highest content of amino acids. Progressive degradation of polypeptide chains was observed in the protein pattern of the extracted gelatin as the time duration of ultrasound extraction increased. Fourier transform infrared (FTIR) spectroscopy depicted loss of molecular order and degradation in UA6. Scanning electron microscopy (SEM) revealed protein aggregation and network formation in the gelatin samples with increasing time of ultrasound treatment. The study indicated that ultrasound assisted gelatin extraction using actinidin exhibited high yield with good quality gelatin.
    Matched MeSH terms: Peptides/chemistry
  10. Machine learning and molecular simulation ascertain antimicrobial peptide against Klebsiella pneumoniae from public database
    Al-Khdhairawi A, Sanuri D, Akbar R, Lam SD, Sugumar S, Ibrahim N, et al.
    Comput Biol Chem, 2023 Feb;102:107800.
    PMID: 36516617 DOI: 10.1016/j.compbiolchem.2022.107800
    Antimicrobial peptides (AMPs) are short peptides with a broad spectrum of antimicrobial activity. They play a key role in the host innate immunity of many organisms. The growing threat of microorganisms resistant to antimicrobial agents and the lack of new commercially available antibiotics have made in silico discovery of AMPs increasingly important. Machine learning (ML) has improved the speed and efficiency of AMP discovery while reducing the cost of experimental approaches. Despite various ML platforms developed, there is still a lack of integrative use of ML platforms for AMP discovery from publicly available protein databases. Therefore, our study aims to screen potential AMPs with antibiofilm properties from databases using ML platforms, followed by protein-peptide molecular docking analysis and molecular dynamics (MD) simulations. A total of 5850 peptides classified as non-AMP were screened from UniProtKB and analyzed using various online ML platforms (e.g., CAMPr3, DBAASP, dPABBs, Hemopred, and ToxinPred). Eight potential AMP peptides against Klebsiella pneumoniae with antibiofilm, non-toxic and non-hemolytic properties were then docked to MrkH, a transcriptional regulator of type 3 fimbriae involved in biofilm formation. Five of eight peptides bound more strongly than the native MrkH ligand when analyzed using HADDOCK and HPEPDOCK. Following the docking studies, our MD simulated that a Neuropeptide B (Peptide 3) bind strongly to the MrkH active sites. The discovery of putative AMPs that exceed the binding energies of the native ligand underscores the utility of the combined ML and molecular simulation strategies for discovering novel AMPs with antibiofilm properties.
    Matched MeSH terms: Peptides/metabolism
  11. Insights into the Pathophysiology of Alzheimer's Disease and Potential Therapeutic Targets: A Current Perspective
    Rajah Kumaran K, Yunusa S, Perimal E, Wahab H, Müller CP, Hassan Z
    J Alzheimers Dis, 2023;91(2):507-530.
    PMID: 36502321 DOI: 10.3233/JAD-220666
    The aging population increases steadily because of a healthy lifestyle and medical advancements in healthcare. However, Alzheimer's disease (AD) is becoming more common and problematic among older adults. AD-related cases show an increasing trend annually, and the younger age population may also be at risk of developing this disorder. AD constitutes a primary form of dementia, an irreversible and progressive brain disorder that steadily damages cognitive functions and the ability to perform daily tasks. Later in life, AD leads to death as a result of the degeneration of specific brain areas. Currently, the cause of AD is poorly understood, and there is no safe and effective therapeutic agent to cure or slow down its progression. The condition is entirely preventable, and no study has yet demonstrated encouraging findings in terms of treatment. Identifying this disease's pathophysiology can help researchers develop safe and efficient therapeutic strategies to treat this ailment. This review outlines and discusses the pathophysiology that resulted in the development of AD including amyloid-β plaques, tau neurofibrillary tangles, neuroinflammation, oxidative stress, cholinergic dysfunction, glutamate excitotoxicity, and changes in neurotrophins level may sound better based on the literature search from Scopus, PubMed, ScienceDirect, and Google Scholar. Potential therapeutic strategies are discussed to provide more insights into AD mechanisms by developing some possible pharmacological agents for its treatment.
    Matched MeSH terms: Amyloid beta-Peptides/metabolism
  12. Electrochemical biosensor for trypsin activity assay based on cleavage of immobilized tyrosine-containing peptide
    Filippova TA, Masamrekh RA, Shumyantseva VV, Latsis IA, Farafonova TE, Ilina IY, et al.
    Talanta, 2023 May 15;257:124341.
    PMID: 36821964 DOI: 10.1016/j.talanta.2023.124341
    In this work, we proposed a biosensor for trypsin proteolytic activity assay using immobilization of model peptides on screen-printed electrodes (SPE) modified with gold nanoparticles (AuNPs) prepared by electrosynthetic method. Sensing of proteolytic activity was based on electrochemical oxidation of tyrosine residues of peptides. We designed peptides containing N-terminal cysteine residue for immobilization on an SPE, modified with gold nanoparticles, trypsin-specific cleavage site and tyrosine residue as a redox label. The peptides were immobilized on SPE by formation of chemical bonds between mercapto groups of the N-terminal cysteine residues and AuNPs. After the incubation with trypsin, time-dependent cleavage of the immobilized peptides was observed by decline in tyrosine electrochemical oxidation signal. The kinetic parameters of trypsin, such as the catalytic constant (kcat), the Michaelis constant (KM) and the catalytic efficiency (kcat/KM), toward the CGGGRYR peptide were determined as 0.33 ± 0.01 min-1, 198 ± 24 nM and 0.0016 min-1 nM-1, respectively. Using the developed biosensor, we demonstrated the possibility of analysis of trypsin specificity toward the peptides with amino acid residues disrupting proteolysis. Further, we designed the peptides with proline or glutamic acid residues after the cleavage site (CGGRPYR and CGGREYR), and trypsin had reduced activity toward both of them according to the existing knowledge of the enzyme specificity. The developed biosensor system allows one to perform a comparative analysis of the protease steady-state kinetic parameters and specificity toward model peptides with different amino acid sequences.
    Matched MeSH terms: Peptides/chemistry
  13. Role of Flavonoids in Management of Various Biological Targets in Alzheimer's Disease: Evidence from Preclinical to Clinical Studies
    Alharbi KS, Javed Shaikh MA, Imam SS, Alshehri S, Ghoneim MM, Almalki WH, et al.
    Curr Med Chem, 2023;30(18):2061-2074.
    PMID: 36415096 DOI: 10.2174/0929867330666221122115212
    More than 10 million people worldwide have Alzheimer's disease (AD), a degenerative neurological illness and the most prevalent form of dementia. AD's progression in memory loss, cognitive deterioration, and behavioral changes are all symptoms. Amyloid-beta 42 (Aβ42), the hyperphosphorylated forms of microtubule-associated tau protein, and other cellular and systemic alterations are all factors that contribute to cognitive decline in AD. Rather than delivering a possible cure, present therapy strategies focus on reducing disease symptoms. It has long been suggested that various naturally occurring small molecules (plant extract products and microbiological isolates, for example) could be beneficial in preventing or treating disease. Small compounds, such as flavonoids, have attracted much interest recently due to their potential to alleviate cellular stress. Flavonoids have been proven helpful in various ways, including antioxidants, anti-inflammatory agents, and anti-apoptotic agents, but their mechanism remains unknown. The flavonoid therapy of Alzheimer's disease focuses on this review, which includes a comprehensive literature analysis.
    Matched MeSH terms: Amyloid beta-Peptides/metabolism
  14. Periodontal health status, Porphyromonas gingivalis and anti-cyclic citrullinated peptide antibodies among rheumatoid arthritis patients
    Wan Jiun T, Taib H, Majdiah Wan Mohamad W, Mohamad S, Syamimee Wan Ghazali W
    Int Immunopharmacol, 2023 Nov;124(Pt B):110940.
    PMID: 37722261 DOI: 10.1016/j.intimp.2023.110940
    Porphyromonas gingivalis (P. gingivalis) is the primary periodontal pathogen involved in protein citrullination, which triggers the production of anti-cyclic citrullinated peptide (anti-CCP) antibodies, exacerbating rheumatoid arthritis (RA). This study aims to evaluate the amount of P. gingivalis and its association with anti-CCP antibodies in RA patients with periodontitis. This cross-sectional study involves 100 RA patients with a mean age of 52.36 (SD 13.90) years. Smokers and patients with other uncontrolled systemic diseases were excluded. Disease Activity Score-28 (DAS-28) was used to determine RA disease severity. Periodontal parameters were examined to determine periodontal status. Subsequently, plaque samples were collected from the subgingival periodontal pocket for assessment of P. gingivalis bacterial load using the loop-mediated isothermal amplification method. Blood samples (5 ml) were obtained from all participants to analyse anti-CCP antibody levels. Data was analysed by using SPSS version 24.0. Most participants were female (85.0%) and had low RA disease severity (62%). The mean RA disease duration was 7.77 (SD 6.3) years, with a mean DAS-28 of 3.17 (SD 1.0). Forty-seven per cent of participants had periodontitis, but all periodontal parameters were not associated with RA disease activity (P = 0.38). P. gingivalis bacterial load ranged from 10 to 109 copies/μl. Fifty-five per cent of the collected samples showed positive anti-CCP antibody levels, but no significant association was observed with the P. gingivalis bacterial load (P = 0.58). Considering the study's limitations, although periodontitis is prevalent among RA patients, there is a lack of association between P. gingivalis bacterial load and anti-CCP antibody levels, which should be investigated further.
    Matched MeSH terms: Peptides; Peptides, Cyclic
  15. A review: Exploring the metabolic and structural characterisation of beta pleated amyloid fibril in human tissue using Raman spectrometry and SAXS
    Mohd Nor Ihsan NS, Abdul Sani SF, Looi LM, Cheah PL, Chiew SF, Pathmanathan D, et al.
    Prog Biophys Mol Biol, 2023 Sep;182:59-74.
    PMID: 37307955 DOI: 10.1016/j.pbiomolbio.2023.06.002
    Amyloidosis is a deleterious condition caused by abnormal amyloid fibril build-up in living tissues. To date, 42 proteins that are linked to amyloid fibrils have been discovered. Amyloid fibril structure variation can affect the severity, progression rate, or clinical symptoms of amyloidosis. Since amyloid fibril build-up is the primary pathological basis for various neurodegenerative illnesses, characterization of these deadly proteins, particularly utilising optical techniques have been a focus. Spectroscopy techniques provide significant non-invasive platforms for the investigation of the structure and conformation of amyloid fibrils, offering a wide spectrum of analyses ranging from nanometric to micrometric size scales. Even though this area of study has been intensively explored, there still remain aspects of amyloid fibrillization that are not fully known, a matter hindering progress in treating and curing amyloidosis. This review aims to provide recent updates and comprehensive information on optical techniques for metabolic and proteomic characterization of β-pleated amyloid fibrils found in human tissue with thorough literature analysis of publications. Raman spectroscopy and SAXS are well established experimental methods for study of structural properties of biomaterials. With suitable models, they offer extended information for valid proteomic analysis under physiologically relevant conditions. This review points to evidence that despite limitations, these techniques are able to provide for the necessary output and proteomics indication in order to extrapolate the aetiology of amyloid fibrils for reliable diagnostic purposes. Our metabolic database may also contribute to elucidating the nature and function of the amyloid proteome in development and clearance of amyloid diseases.
    Matched MeSH terms: Amyloid beta-Peptides/chemistry
  16. Behavioural Effects and RNA-seq Analysis of Aβ42-Mediated Toxicity in a Drosophila Alzheimer's Disease Model
    Tan FHP, Azzam G, Najimudin N, Shamsuddin S, Zainuddin A
    Mol Neurobiol, 2023 Aug;60(8):4716-4730.
    PMID: 37145377 DOI: 10.1007/s12035-023-03368-x
    Alzheimer's disease (AD) is the most common neurological ailment worldwide. Its process comprises the unique aggregation of extracellular senile plaques composed of amyloid-beta (Aβ) in the brain. Aβ42 is the most neurotoxic and aggressive of the Aβ42 isomers released in the brain. Despite much research on AD, the complete pathophysiology of this disease remains unknown. Technical and ethical constraints place limits on experiments utilizing human subjects. Thus, animal models were used to replicate human diseases. The Drosophila melanogaster is an excellent model for studying both physiological and behavioural aspects of human neurodegenerative illnesses. Here, the negative effects of Aβ42-expression on a Drosophila AD model were investigated through three behavioural assays followed by RNA-seq. The RNA-seq data was verified using qPCR. AD Drosophila expressing human Aβ42 exhibited degenerated eye structures, shortened lifespan, and declined mobility function compared to the wild-type Control. RNA-seq revealed 1496 genes that were differentially expressed from the Aβ42-expressing samples against the control. Among the pathways that were identified from the differentially expressed genes include carbon metabolism, oxidative phosphorylation, antimicrobial peptides, and longevity-regulating pathways. While AD is a complicated neurological condition whose aetiology is influenced by a number of factors, it is hoped that the current data will be sufficient to give a general picture of how Aβ42 influences the disease pathology. The discovery of molecular connections from the current Drosophila AD model offers fresh perspectives on the usage of this Drosophila which could aid in the discovery of new anti-AD medications.
    Matched MeSH terms: Amyloid beta-Peptides/metabolism
  17. Characterization and determination of casein glycomacropeptide in dairy products by UHPLC-MS/MS based on its characteristic peptide
    Chen Q, Lai S, Dong L, Liu Y, Pan D, Wu Z, et al.
    Food Chem, 2024 Jan 01;430:137049.
    PMID: 37544157 DOI: 10.1016/j.foodchem.2023.137049
    The ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS) method was built to quantify the casein glycomacropeptide (CGMP) in bovine dairy products accurately based on targeted proteomics. Qualitative analysis of theoretical peptides was carried out using high-resolution mass spectrometry (HRMS) and protein software. Isotope-labeled characteristic peptides were acquired via the labeled amino acid condensation method to correct the matrix effects. Peptide MAIPPK was the representative characteristic peptide for distinguishing the CGMP from κ-casein through trypsin digestion. After optimizing the pre-treatment conditions, the final 8% oxidant concentration was selected and the 10% formic acid concentration with 2.5 h oxidation time. Moreover, the results of methodological verification showed that the recovery rate was 103.7%, meanwhile the precision of inter-day and intra-day was less than 5%. In conclusion, the research demonstrated the characteristic peptide MAIPPK could quantitatively applied to detect CGMP in dairy products.
    Matched MeSH terms: Peptides/chemistry
  18. Pediococcus pentosaceus LAB6- and Lactiplantibacillus plantarum LAB12-Derived Cell Free Supernatant Inhibited RhoA Activation and Reduced Amyloid-Β In Vitro
    Zaki RM, Ramasamy K, Ahmad Alwi NA, Mohd Yusoff R, Lim SM
    Probiotics Antimicrob Proteins, 2024 Feb;16(1):62-75.
    PMID: 36443559 DOI: 10.1007/s12602-022-10009-7
    Alzheimer's disease (AD) is characterized by aggregation of amyloid beta (Aβ) plaque. RhoA may serve as a potential target for prevention against AD given its role in the amyloidogenic pathway. The recent emergence of the gut-brain axis has linked lactic acid bacteria (LAB) to neuroprotection against AD. This study assessed the importance of RhoA inhibition in mediating the neuroprotective potential of LAB. To this end, de Man, Rogosa and Sharpe (MRS) broth fermented by lactobacilli or pediococci were tested against SK-N-SH (a human neuroblastoma cell line) in the presence of RhoA activator II for 24 h after which the RhoA activity was measured using the G-LISA Kit. Fluorescence staining of f-actin stress fibres was performed to validate RhoA inhibition. SK-N-SH was transfected with plasmid expressing amyloid precursor protein (APP) gene. The Aβ concentration in transfected cells exposed to LAB-derived cell free supernatant (CFS) in the presence of RhoA activator II was measured using the ELISA kit. Furthermore, this study measured organic acids in LAB-derived CFS using the gas chromatography. It was found that LAB-derived CFS yielded strain-dependent inhibition of RhoA, with LAB6- and LAB12-derived CFS being the most potent Pediococcal- and Lactiplantibacillus-based RhoA inhibitor, respectively. Lesser stress fibres were formed under treatment with LAB-derived CFS. The LAB-derived CFS also significantly inhibited Aβ in SK-N-SH transfected with APP gene in the presence of RhoA activator II. The LAB-derived CFS was presented with increased lactic acid, acetic acid, butyric acid and propionic acid. The present findings warrant in-depth study using animal models.
    Matched MeSH terms: Amyloid beta-Peptides/metabolism
  19. Leakage beyond the primary lesion: A temporal analysis of cerebrovascular dysregulation at sites of hippocampal secondary neurodegeneration following cortical photothrombotic stroke
    Hood RJ, Sanchez-Bezanilla S, Beard DJ, Rust R, Turner RJ, Stuckey SM, et al.
    J Neurochem, 2023 Dec;167(6):733-752.
    PMID: 38010732 DOI: 10.1111/jnc.16008
    We have previously demonstrated that a cortical stroke causes persistent impairment of hippocampal-dependent cognitive tasks concomitant with secondary neurodegenerative processes such as amyloid-β accumulation in the hippocampus, a region remote from the primary infarct. Interestingly, there is emerging evidence suggesting that deposition of amyloid-β around cerebral vessels may lead to cerebrovascular structural changes, neurovascular dysfunction, and disruption of blood-brain barrier integrity. However, there is limited knowledge about the temporal changes of hippocampal cerebrovasculature after cortical stroke. In the current study, we aimed to characterise the spatiotemporal cerebrovascular changes after cortical stroke. This was done using the photothrombotic stroke model targeting the motor and somatosensory cortices of mice. Cerebrovascular morphology as well as the co-localisation of amyloid-β with vasculature and blood-brain barrier integrity were assessed in the cortex and hippocampal regions at 7, 28 and 84 days post-stroke. Our findings showed transient cerebrovascular remodelling in the peri-infarct area up to 28 days post-stroke. Importantly, the cerebrovascular changes were extended beyond the peri-infarct region to the ipsilateral hippocampus and were sustained out to 84 days post-stroke. When investigating vessel diameter, we showed a decrease at 84 days in the peri-infarct and CA1 regions that were exacerbated in vessels with amyloid-β deposition. Lastly, we showed sustained vascular leakage in the peri-infarct and ipsilateral hippocampus, indicative of a compromised blood-brain-barrier. Our findings indicate that hippocampal vasculature may represent an important therapeutic target to mitigate the progression of post-stroke cognitive impairment.
    Matched MeSH terms: Amyloid beta-Peptides/metabolism
  20. Antiviral activity of SP81 peptide against Enterovirus A71 (EV-A71)
    Abd-Aziz N, Lee MF, Ong SK, Poh CL
    Virology, 2024 Jan;589:109941.
    PMID: 37984152 DOI: 10.1016/j.virol.2023.109941
    The hand, food, and mouth disease (HFMD) is primarily caused by Enterovirus A71 (EV-A71). EV-A71 outbreaks in the Asia Pacific have been associated with severe neurological disease and high fatalities. Currently, there are no FDA-approved antivirals for the treatment of EV-A71 infections. In this study, the SP81 peptide, derived from the VP1 capsid protein of EV-A71 was shown to be a promising antiviral candidate for the treatment of EV-A71 infections. SP81 peptide was non-toxic to RD cells up to 45 μM, with a half-maximal cytotoxic concentration (CC50) of 90.32 μM. SP81 peptide exerted antiviral effects during the pre- and post-infection stages with 50% inhibitory concentrations (IC50) of 4.529 μM and 1.192 μM, respectively. Direct virus inactivation of EV-A71 by the SP81 peptide was also observed with an IC50 of 8.076 μM. Additionally, the SP81 peptide exhibited direct virus inactivation of EV-A71 at 95% upon the addition of the SP81 peptide within 5 min. This study showed that the SP81 peptide exhibited significant inhibition of EV-A71 and could serve as a promising antiviral agent for further clinical development against EV-A71 infections.
    Matched MeSH terms: Peptides/pharmacology
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